ArticleMolecular and cellular biology2011
NF-kappaB protects cells from gamma interferon-induced RIP1-dependent necroptosis.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 2 of them syntheses that pooled it.
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Who cites it
83 citing papers in PubMed, 2 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- Deflazacort vs prednisone treatment for Duchenne muscular dystrophy: A meta-analysis of disease progression rates in recent multicenter clinical trials.Muscle & nerve · 2020Pooled it
- Pooled it
- Toripalimab plus chemotherapy and radiotherapy for treatment-naive advanced esophageal squamous cell carcinoma: a single-arm phase 2 trial.Nature communications · 2024Trial
- Cytokine-induced senescence in tumors is based on sustained activation of STAT1- and NFκB-dependent gene regulatory signatures.GeroScience · 2026Article
- Capecitabine combined with fecal microbiota transplantation prevents colorectal cancer progression through correction of microbial dysbiosis and immune regulation.Scientific reports · 2026Article
- RIPK1 regulates β-cell fate via actions on gene expression and kinase signaling in a mouse model of β-cell self-reactivity.Cell death & disease · 2026Article
- Atherosclerotic-dose TMAO accentuates redox imbalances and motor dysfunctions in a MPTP mouse model of Parkinson's disease.Frontiers in aging neuroscience · 2026Article
- A viral necrosome mediates direct RIPK3 activation to promote inflammatory necroptosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The immune checkpoint regulator CD40 potentiates myocardial inflammation.Nature cardiovascular research · 2025Article
- Review
- Role and mechanism of gut microbiota in regulating interferon-mediated programmed cell death in colorectal cancer.Frontiers in immunology · 2025Review
- FOXA1 enhances antitumor immunity via repressing interferon-induced PD-L1 expression in nasopharyngeal carcinoma.Journal for immunotherapy of cancer · 2024Article
- IFNγ-Induced Bcl3, PD-L1 and IL-8 Signaling in Ovarian Cancer: Mechanisms and Clinical Significance.Cancers · 2024Review
- Psilocybin and Eugenol Reduce Inflammation in Human 3D EpiIntestinal Tissue.Life (Basel, Switzerland) · 2023Article
- ERK mediates interferon gamma-induced melanoma cell death.Molecular cancer · 2023Article
- The role of IFN-γ-signalling in response to immune checkpoint blockade therapy.Essays in biochemistry · 2023Review
- A new strategy for treating colorectal cancer: Regulating the influence of intestinal flora and oncolytic virus on interferon.Molecular therapy oncolytics · 2023Review
- In vitro CRISPR screening uncovers CRTC3 as a regulator of IFN-γ-induced ferroptosis of hepatocellular carcinoma.Cell death discovery · 2023Article
- NF-κB in Cell Deaths, Therapeutic Resistance and Nanotherapy of Tumors: Recent Advances.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Manipulation of Host Cell Death Pathways by Herpes Simplex Virus.Current topics in microbiology and immunology · 2023Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Interferons (IFNs) are cytokines with well-described immunomodulatory and antiviral properties, but less is known about the mechanisms by which they promote cell survival or cell death. Here, we show that IFN-γ induces RIP1 kinase-dependent necroptosis in mammalian cells deficient in NF-κB signaling. Induction of necroptosis by IFN-γ was found to depend on Jak1 and partially on STAT1. We also demonstrate that IFN-γ activates IκB kinase β (IKKβ)-dependent NF-κB to regulate a transcriptional program that protects cells from necroptosis. IFN-γ induced progressive accumulation of reactive oxygen species (ROS) and eventual loss of mitochondrial membrane potential in cells lacking the NF-κB subunit RelA. Whole-genome microarray analyses identified sod2, encoding the antioxidant enzyme manganese superoxide dismutase (MnSOD), as a RelA target and potential antinecroptotic gene. Overexpression of MnSOD inhibited IFN-γ-mediated ROS accumulation and partially rescued RelA-deficient cells from necroptosis, while RNA interference (RNAi)-mediated silencing of sod2 expression increased susceptibility to IFN-γ-induced cell death. Together, these studies demonstrate that NF-κB protects cells from IFN-γ-mediated necroptosis by transcriptionally activating a survival response that quenches ROS to preserve mitochondrial integrity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.